This proposal aims at further evaluation of an inhibitor of C3 conversion which appears during allotransplantation rejection. The relationship of this material to the biology of the complement system, lymphocyte activity, and cellular death will be of central focus. In studying the mechanisms of action of the inhibitor in complement activity, the primary objectives will be the isolation and physicochemical characterization of this material, the physicochemical effects of the inhibitor on native and bound C3, the effect of the inhibitor in promoting the alternate pathway of complement activation and the effect of the inhibitor as a regulator of the biologic activity of bound C3. In elucidating the role of the inhibitor in lymphocyte function, the focus will be on the physicochemical means by which the inhibitor blocks the C3 receptor site on B-type cells and the effect on several lymphocyte functions, most particularly that of cytotoxicity. Finally, the role of the inhibitor in rejection per se will be studied by evaluating the relationship of the inhibitor to cytotoxic antibody, mixed lymphocyte culture activity, as well as certain other lymphocyte function studies. Further correlation between clinical rejection and the appearance of the inhibitor in the circulation will be pursued in both kidney and heart experimental allografts as well as in human kidney transplant recipients.